Carrier-Free Self-Assembled Nanoparticles for Triple-Amplified Tumor Chemodynamic Therapy and Cuproptosis Induction

Chemodynamic therapy (CDT) holds great promise in cancer treatment, whereas its efficacy is severely compromised by the low concentration of endogenous hydrogen peroxide(H₂O₂), insufficient exogenous catalytic ions, and the presence of high levels of cellular glutathione (GSH). Herein, a dissociable, tumor cell membrane-camouflaged carrier-free nanoparticle is developed through the molecular interaction of copper ions (Cu²⁺), dequalinium (DQ), and β-Lapachone (β-Lap). Upon homotypic tumor targeting, the system releases Cu²⁺ (exogenous catalytic ions), β-Lap (H₂O₂ donor), and DQ (GSH scavenger), achieving triple amplification of CDT efficacy. Concurrently, the intracellular accumulation of Cu²⁺ induces cuproptosis, thereby synergistically augmenting CDT efficacy and strikingly restraining tumor growth. Overall, the integration of Cu²⁺ supplementation, H₂O₂ self-supplying, and GSH depletion offers a promising avenue for improving cancer treatment outcomes and paves a new way for multimodal cancer therapy.